BAIBA mimics the role of exercise through a few interrelated pathways.
So when a person exercises, concentrations of BAIBA dramatically increase within both skeletal muscle and within other tissues.[1,3] BAIBA then signals for an increase in the expression of brown adipocyte-specific genes via PPAR alpha, which triggers the “browning of white fat”.[1]
Brown adipose cells generates heat from fat, increasing the body’s metabolism and therefore expending more calories during rest and exercise.
BAIBA is a naturally occurring amino acid, a product of the metabolism of thymine and valine. [1][2]
Levels of BAIBA are increased significantly by endurance exercise, a result of PGC1α-mediated amino acid breakdown. [3]
Target(s):
• BAIBA exerts its effects on hepatocytes (liver cells) and white adipocytes (fat cells) through PPARalpha (PPARα). [4] PPARα regulates the use of fat as a source of energy. [5]
Research summary:
• Activation of PPARα in the liver and adipose tissue promotes lipolysis and beta oxidation of fatty acids. [5]
• PPARα activation stimulates white fat cell precursors to differentiate into beige/brite adipocytes. [4]
• PPARα agonism also induces mature white adipocytes to develop a beige/brite phenotype. [4]
• PPARα agonists increase UCP-1 mRNA levels in brown fat. [6]
• PPARα agonism in the small intestine is thought to be involved in the regulation of satiety (lack of hunger). [7][8]
• Coadministered PPARα and β3 adrenoceptor agonists may have a synergistic effect on the browning of white fat and UCP1-mediated thermogenesis. [9]
• BAIBA induces human stem cells, under conditions that would normally result in white adipocyte differentiation, instead to express brown-fat specific genes like UCP-1. [4]
• BAIBA induced increased expression of brown/beige fat-specific genes in an in vivo experiment on mice. [4]
• BAIBA levels are increased after endurance exercise, and may be responsible for some of the metabolic benefits of exercise. [4]
• BAIBA increases hepatic fatty acid oxidation and decreases fat mass in mice [10]
• Some of the fat-loss effects of thymine-based prescription drugs in humans may be due to an increase in utilization of free fatty acids resulting from the production of BAIBA as a metabolite. [10]
• Rats and mice treated with BAIBA and other PPARα agonists lose more body fat and gain less body weight than control animals. [11][7][9][10][4]
Cold Temperatures and beta-adrenergic hormones
The thermogenic effects of brown fat can be activated in several ways; in hibernating animals and babies the trigger is cold temperatures. Cold temperatures trigger a release of norepinephrine into the blood stream, an adrenergic hormone which has several important roles, one of which is to activate brown fat via the beta-3 adrenergic receptor (β3 adrenoreceptor).
Unlike other beta adrenergic receptors, which are widely distributed about the body, being found in cardiac tissue, skeletal and smooth muscle, and adipose tissue, distribution of β3 receptors are restricted to a few tissues – including brown fat, where activation increases energy expenditure.
Brown fat also expresses heat-sensing receptors of its own. The receptor that detects cold temperatures is the cold and menthol receptor 1 (CMR1), more formally known as the transient receptor potential cation channel subfamily M member 8 (TRPM8).The transient receptor potential channels (TRPs) help the peripheral nervous system detect important variations in temperature; TRPV1 detects and regulates heat, but can also be activated by things like capsaicin (which is why chili peppers taste hot), and TRPM8 detects cold but can also be activated by compounds like menthol (which is why peppermint tastes cold).
Thermogenesis in brown fat can be triggered by TRPM8 activation or norepinephrine release (β3 adrenoreceptor agonism). Human white adipose tissue also expresses the cold-sensing receptor TRPM8, which, when activated, transdifferentiates to a brown-like phenotype expressing UCP-1.
So when a person exercises, concentrations of BAIBA dramatically increase within both skeletal muscle and within other tissues.[1,3] BAIBA then signals for an increase in the expression of brown adipocyte-specific genes via PPAR alpha, which triggers the “browning of white fat”.[1]
Brown adipose cells generates heat from fat, increasing the body’s metabolism and therefore expending more calories during rest and exercise.
- Converting to a hybrid fat with the best of both worlds
Interestingly, however, BAIBA doesn’t turn white fat completely brown but instead turns it into a third type known as “beige” fat.[1,10] This adipose form has the characteristics of brown fat but exists within white fat cells, thus allowing for heat generation from within the stored fat.[10]
BAIBA also influences liver fat burning and cholesterol regulation through PPAR alpha activation: when PPAR alpha is activated, it increases the expression of lipoprotein lipaseand apolipoprotein A-V, and decreases expression of apoC-III in the liver.[11,12]
These three changes allow the breakdown of triglycerides and cholesterol and the transport of fatty acids out of the liver to be either stored again or burned for energy.
Going further, PPAR alpha activation also increases hepatic apoA-I and apoA, which increases levels of the ‘good’ cholesterol, HDL.[11,12]
BAIBA is a naturally occurring amino acid, a product of the metabolism of thymine and valine. [1][2]
Levels of BAIBA are increased significantly by endurance exercise, a result of PGC1α-mediated amino acid breakdown. [3]
Target(s):
• BAIBA exerts its effects on hepatocytes (liver cells) and white adipocytes (fat cells) through PPARalpha (PPARα). [4] PPARα regulates the use of fat as a source of energy. [5]
Research summary:
• Activation of PPARα in the liver and adipose tissue promotes lipolysis and beta oxidation of fatty acids. [5]
• PPARα activation stimulates white fat cell precursors to differentiate into beige/brite adipocytes. [4]
• PPARα agonism also induces mature white adipocytes to develop a beige/brite phenotype. [4]
• PPARα agonists increase UCP-1 mRNA levels in brown fat. [6]
• PPARα agonism in the small intestine is thought to be involved in the regulation of satiety (lack of hunger). [7][8]
• Coadministered PPARα and β3 adrenoceptor agonists may have a synergistic effect on the browning of white fat and UCP1-mediated thermogenesis. [9]
• BAIBA induces human stem cells, under conditions that would normally result in white adipocyte differentiation, instead to express brown-fat specific genes like UCP-1. [4]
• BAIBA induced increased expression of brown/beige fat-specific genes in an in vivo experiment on mice. [4]
• BAIBA levels are increased after endurance exercise, and may be responsible for some of the metabolic benefits of exercise. [4]
• BAIBA increases hepatic fatty acid oxidation and decreases fat mass in mice [10]
• Some of the fat-loss effects of thymine-based prescription drugs in humans may be due to an increase in utilization of free fatty acids resulting from the production of BAIBA as a metabolite. [10]
• Rats and mice treated with BAIBA and other PPARα agonists lose more body fat and gain less body weight than control animals. [11][7][9][10][4]
Cold Temperatures and beta-adrenergic hormones
The thermogenic effects of brown fat can be activated in several ways; in hibernating animals and babies the trigger is cold temperatures. Cold temperatures trigger a release of norepinephrine into the blood stream, an adrenergic hormone which has several important roles, one of which is to activate brown fat via the beta-3 adrenergic receptor (β3 adrenoreceptor).
Unlike other beta adrenergic receptors, which are widely distributed about the body, being found in cardiac tissue, skeletal and smooth muscle, and adipose tissue, distribution of β3 receptors are restricted to a few tissues – including brown fat, where activation increases energy expenditure.
Brown fat also expresses heat-sensing receptors of its own. The receptor that detects cold temperatures is the cold and menthol receptor 1 (CMR1), more formally known as the transient receptor potential cation channel subfamily M member 8 (TRPM8).The transient receptor potential channels (TRPs) help the peripheral nervous system detect important variations in temperature; TRPV1 detects and regulates heat, but can also be activated by things like capsaicin (which is why chili peppers taste hot), and TRPM8 detects cold but can also be activated by compounds like menthol (which is why peppermint tastes cold).
Thermogenesis in brown fat can be triggered by TRPM8 activation or norepinephrine release (β3 adrenoreceptor agonism). Human white adipose tissue also expresses the cold-sensing receptor TRPM8, which, when activated, transdifferentiates to a brown-like phenotype expressing UCP-1.
